Electrospun ceramic-polymer composite as a scaffold for tissue repair

• US 9,181,636 B2
• Filed: 08/16/2011
• Issued: 11/10/2015
• Est. Priority Date: 06/18/2007
• Status: Active Grant

• Current Assignee: New Jersey Institute of Technology
• Original Assignee: New Jersey Institute of Technology
• Inventors: Arinzeh, Treena Lynne
• Primary Examiner(s): Tran, Susan
• Assistant Examiner(s): CRAIGO, WILLIAM A
• Application Number:
  US13/210,806
• Publication Number:
  US 20110300626A1
• Time in Patent Office: 1,547 Days
• US Class Current: 1/1
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2/3094 Designing or manufacturing processes
• CPC Class Codes: A61F 2002/4495 having a fabric structure, e.g. made from wires or fibres
• CPC Class Codes: A61F 2240/001 Designing or manufacturing processes
• CPC Class Codes: A61F 2310/00179 Ceramics or ceramic-like structures
• CPC Class Codes: A61L 27/3821 Bone-forming cells, e.g. osteoblasts, osteocytes, osteoprogenitor cells
• CPC Class Codes: A61L 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/3847 Bones
• CPC Class Codes: A61L 27/46 with phosphorus-containing inorganic fillers
• CPC Class Codes: D01D 5/0007 Electro-spinning non-woven fabrics produced by electro-spinning D04H1/728
• CPC Class Codes: D01F 1/10 Other agents for modifying properties

Abstract

The present invention relates to compositions and methods of preparing a three-dimensional matrix of micron sized electrospun fibers, wherein the electrospun fibers are formed from a electrospun composite comprising a bioactive ceramic component and a polymer component. The matrix provides an osteoconductive and osteoinductive scaffold supporting osteogenesis and thereby facilitates bone repair.

Claims

1. A method of preparing an osteoinductive and osteoconductive scaffold to facilitate bone repair, the method comprising the steps:

(a) preparing a ceramic-polymer solution comprising a bioactive ceramic component comprising from about 10-50% (w/w) of a 20;

80 ratio of hydroxyapatite (HA)/tricalcium phosphate (TCP), and a polymer component comprising from about 50-90% (w/w) of polycaprolactone (PCL) dissolved in a solvent selected from the group consisting of methylene chloride (MC), dimethyl formamide (DFM), and a combination thereof; and

(b) electrospinning the ceramic-polymer solution, and thereby forming a ceramic-polymer composite, and depositing a three-dimensional nonwoven matrix of micron sized electrospun fibers comprising the ceramic-polymer composite on a collector, the three dimensional-nonwoven matrix of electrospun fibers including a plurality of micron sized pores, each micron sized pore of the plurality of micron sized pores having a pore size of at least about 20 microns in diameter.

2. The method according to claim 1, wherein the composite contains at least 10% by weight of the ceramic component.

3. The method according to claim 1, wherein the composite contains at least about 60% by weight of a polymer component.

4. The method according to claim 1, wherein the composite contains at least 10% by weight of the ceramic component and at least about 60% by weight of the polymer component.

5. The method according to claim 1, wherein the polymer component of the composite of step (a) further includes at least one polymer selected from the group consisting of a nondegradable polymer and a degradable polymer.

6. The method according to claim 5, wherein the nondegradable polymer is selected from the group consisting of a polyurethane, a polyvinylidine fluoride, and a polyvinylidine fluoride trifluoroethylene.

7. The method according to claim 5, wherein the degradable polymer is selected from the group consisting of poly(lactic acid-glycolic acid), poly(lactic acid), poly(glycolic acid), a poly(orthoester), a poly(phosphazene), a polyamide, a polysaccharide, and a collagen.

8. The method according to claim 1, further comprising the steps:

(c) seeding the three-dimensional nonwoven matrix of electrospun fibers with isolated differentiable human mesenchymal cells or osteoblasts; and

(d) growing the differentiable human mesenchymal cells or osteoblasts on the three-dimensional nonwoven matrix of electrospun fibers so that the differentiable human mesenchymal cells or osteoblasts differentiate into a mature cell phenotype on the scaffold.

9. The method according to claim 1, wherein the electrospun fibers in the matrix are characterized by a mean fiber diameter of at least about 20 microns.

10. The method according to claim 1, wherein the electrospun fibers in the matrix are characterized by a mean inter-fiber distance of at least about 90 microns.

11. The method according to claim 1, wherein the micron sized pores are characterized by a mean pore size of at least 80 microns.

12. The method according to claim 1, wherein step (b) includes electrospinning the ceramic-polymer solution at a rate of about 0.1 ml/min at an electrostatic potential of 17 kV, and at a collector-to-needle distance of 15 cm.